Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice.
Increased expression of glial fibrillary acidic protein (GFAP) is a hallmark of gliosis, the astrocytic hypertrophy that occurs during a wide variety of diseases of the central nervous system. To determine whether this increase in GFAP expression per se alters astrocyte function, we generated transgenic mice that carry copies of the human GFAP gene driven by its own promoter. Astrocytes of these mice are hypertrophic, up-regulate small heat-shock proteins, and contain inclusion bodies identical histologically and antigenically to the Rosenthal fibers of Alexander's disease. Mice in the highest expressing lines die by the second postnatal week. The results support the notion that Alexander's disease is a disorder of astrocytes, and provide an animal model for studying the causes and consequences of inclusion body disease.
Messing
A
A
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 53706, USA. amessing@svm.vetmed.wisc.edu
Head
M W
MW
Galles
K
K
Galbreath
E J
EJ
Goldman
J E
JE
Brenner
M
M
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D001927:Brain Diseases / Q000473:pathology*; D003459:Crystallins / Q000235:genetics / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics* / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D006984:Hypertrophy; D002479:Inclusion Bodies / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
D003459:Crystallins; D005904:Glial Fibrillary Acidic Protein; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D012333:RNA, Messenger